ENST00000618612.5:c.190T>C

Variant names:

• chr20-1372136-A-G
• ENST00000618612.5:c.190T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000618612.5(FKBP1A):​c.190T>C​(p.Cys64Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C64S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FKBP1A ENST00000618612.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.425
• Publications: 0 publications found

Genes affected

FKBP1A (HGNC:3711): (FKBP prolyl isomerase 1A) The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels, and coordinates multi-protein complex formation of the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. Multiple alternatively spliced variants, encoding the same protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed. [provided by RefSeq, Sep 2008]

SDCBP2-AS1 (HGNC:44314): (SDCBP2 antisense RNA 1)

ENSG00000274322 (HGNC:):

FKBP1A-SDCBP2 (HGNC:41997): (FKBP1A-SDCBP2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring FK506 binding protein 1A, 12kDa and syndecan binding protein (syntenin) 2 genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20102686).
• BP6: Variant 20-1372136-A-G is Benign according to our data. Variant chr20-1372136-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3095310.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000618612.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1A	NM_000801.5	MANE Select	c.303T>C	p.Asp101Asp	synonymous	Exon 4 of 5	NP_000792.1	P62942
	FKBP1A	NM_001199786.2		c.190T>C	p.Cys64Arg	missense	Exon 3 of 4	NP_001186715.1	A0A087WTS4
	FKBP1A	NM_054014.4		c.303T>C	p.Asp101Asp	synonymous	Exon 4 of 4	NP_463460.1	P62942

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1A	ENST00000618612.5	TSL:1	c.190T>C	p.Cys64Arg	missense	Exon 3 of 4	ENSP00000478093.1	A0A087WTS4
	FKBP1A	ENST00000400137.9	TSL:1 MANE Select	c.303T>C	p.Asp101Asp	synonymous	Exon 4 of 5	ENSP00000383003.4	P62942
	FKBP1A	ENST00000381719.8	TSL:1	c.303T>C	p.Asp101Asp	synonymous	Exon 4 of 4	ENSP00000371138.3	P62942

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.86
DANN	Benign	0.71
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.20	T
PhyloP100		-0.42
Sift4G	Uncertain	0.021	D
Vest4		0.32
MVP		0.74
GERP RS		-6.9
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr20-1352780;